The overall objective of this project is to develop a replacement for heparin that can be orally administered. Heparin is currently the drug of choice for the prophylaxis and initial therapy of thromboembolic disease. It produces an immediate anticoagulant effect when present in plasma and can be administered intravenously or subcutaneously (but not orally). Bleeding and thrombocytopenia are toxicities associated with heparin therapy. This proposal addresses the lack of alternative drugs for acute anticoagulation. During the Phase I gram period we synthesized sulfated bis-disaccharide acid amides that have in vitro anticoagulant and antithrombotic activities. The most active compound, synthesized from maltobionic acid with a unique linker demonstrated in vivo anticoagulant activity within IS minutes of oral administration in rabbits and lasted for over eight hours. We have been awarded a patent for this compound. We propose to continue the testing of this maltobionic acid derivative in vivo and to identify its mechanism of action and study its pharmacodynamics. The advantages of this compound for clinical use would include ease of administration , rapid onset of action and chemical homogeneity, which could reduce or eliminate the toxicities associated with heparin therapy. PROPOSED COMMERCIAL APPLICATIONS: The ability to offer alternate drugs to replace Heparin in treating thromboembolic disease is of major medical and commercial significance.